Diabetes is one of the metabolic diseases characterized by high blood glucose level caused by abnormal glucose metabolism. This disease is largely classified into type 1 diabetes also called insulin dependency diabetes or IDDM, and type 2 diabetes also called non-insulin dependent diabetes or NIDDM. Diabetes not only causes microvascular complications (e.g., diabetic retinopathy, diabetic neuropathy, diabetic nephropathy) but also is a risk factor of macroangiopathy (e.g., arteriosclerosis, cardiovascular disease, myocardial infarction).
GPR119 is a G protein-coupled receptor strongly expressed in pancreatic B cells, and has been reported in recent years to function as a blood glucose sensor that promotes insulin secretion in a blood glucose level-dependent manner (see non-patent document 1). Therefore, GPR119 is drawing attention as a new target molecule for diabetes treatment.
It has also been reported that GPR119 is expressed in human or mouse intestine, and a GPR119 agonist promotes GLP-1 and GIP secretion in mouse (see non-patent document 2), and that a GPR119 agonist promotes PYY or glucagon secretion in mouse (see non-patent document 3).
Accordingly, a compound having a GPR119 agonist action is useful for the prophylaxis or treatment of diabetes, obesity and the like.
In the meantime, the following compounds have been reported.
(1) A compound represented by the formula:
whereinA, B and D are each independently CR4b or N wherein at least one of A, B and D is N,E is CR9R9, CR9, O, N or NH,G is CH or N,J is CR9R9, CR9, CO, CS or N,Y is NR3, O or S,n2 and n3 are each independently an integer of 0 to 2,n4 is an integer of 0 to 3,R1 is optionally substituted aryl or optionally substituted heteroaryl,R2 is optionally substituted aryl, optionally substituted heteroaryl, —COR5, —COOR5 or the like, andR3 is a hydrogen atom, alkyl, alkoxy, cycloalkyl, heteroaryl, heterocyclyl or the like(see patent document 1).(2) A compound represented by the formula:
whereinring A is aryl or heteroaryl,m is an integer of 1 to 3,R1 is acyl, acylsulfonamide, C1-6 alkylsulfonyl or the like,L and J are each independently CH or N,n is an integer of 0 to 4,R7 is C1-6 alkyl,q is an integer of 0 to 2,R8 is C1-6 alkyl, amino or the like,p is an integer of 0 to 2,R9 is C1-6 alkyl, C1-6 alkoxy or the like,X is NR4, O, S, S(O) or S(O)2,R4 is a hydrogen atom or C1-6 alkyl,R2 is —Yt—R5,Y is C(O), C(O)O, C(S), C(S)S, C(S)O or C(O)S,t is an integer of 0 to 1, andR5 is a hydrogen atom, optionally substituted acylalkylene, C1-6 alkyl or the like(see patent document 2).(3) A compound represented by the formula:
whereinA and B are each independently an optionally substituted C1-3 alkylene,D is O, S, S(O), S(O)2, CR2R3 or NR2,E is N, C or CR4,V1 is a bond, optionally substituted C1-3 alkylene or the like,V2 is a bond, optionally substituted C3-6 cycloalkylene or optionally substituted C1-3 alkylene,W is NRS, O, S, S(O) or S(O)2, or absent,Q is NR6, O, S, S(O) or S(O)2.X is N or CR7,Y is N or CR8,Ar1 is optionally substituted aryl or optionally substituted heteroaryl, andR2 is aryl, heteroaryl, carboxy, -G-R22 wherein G is —C(O)—, —COO— or the like, or the like(see patent document 3).(4) A compound represented by the formula:
whereinX1 is N or CR3,X2 and X4 are each independently N or CR4,X5 and X6 are each independently N or CR6,X3 is
R1 is optionally substituted 5- to 7-membered ring,R2 is optionally substituted C1-6 alkyl, optionally substituted 5- to 7-membered monocycle or optionally substituted 6- to 11-membered bicycle,R3, R4 and R5 are each independently a hydrogen atom, a halogen atom, C1-4 haloalkyl or the like, andR6 is a hydrogen atom, C1-6 alkyl, C1-4 haloalkyl or the like(see patent document 4).(5) A compound represented by the formula:
whereinring A is pyrrole, pyrazole, imidazole or triazole,ring B is benzene, pyridine or pyrimidine,ring M is azetidine, pyrrolidine or piperidine,E is a bond or optionally substituted C1-4 alkylene,Z is a hydrogen atom, —CORa, —CO2Ra, optionally substituted phenyl, optionally substituted heteroaryl or the like,R1 and R2 are each independently a hydrogen atom, a halogen atom, cyano, C1-6 alkyl or the like,R3 is a hydrogen atom, C1-6 alkyl or the like,R4 is a hydrogen atom, C1-6 alkoxy, oxo or the like,Ra is a hydrogen atom, optionally substituted C1-6 alkyl, optionally substituted aryl, optionally substituted heteroaryl or the like(see patent document 5).(6) A compound represented by the formula:
whereinR1 is indolin-1-yl mono-substituted by —OR2, —NHR2 or SO2CH3,R2 is aryl optionally substituted by halogen, lower alkyl, alkoxy or the like, monocyclic heteroaryl optionally substituted by halogen, SO2CH3, lower alkyl or the like, or the like,R3 is cyclohexane substituted by oxadiazole substituted by lower alkyl, or piperidine wherein the nitrogen is substituted by R4,R4 is benzyl optionally substituted by cyano, alkoxy or the like, —C(O)—O-lower alkyl, or the like,R5 is hydrogen, NH2, alkoxy, halogen or lower alkyl, andR6 is hydrogen or lower alkyl(see patent document 6).(7) A compound represented by the formula:
whereinp is 1 or 2,R1 is a C1-C6 alkyl group optionally having 1 to 3 substituents selected from substituent group α, a C3-C7 cycloalkyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkynyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkenyl group optionally having 1 to 3 substituents selected from substituent group β, an amino group or a mono- or di-(C1-C6 alkyl)amino group,substituent group α is the group consisting of a halogen atom, a hydroxyl group, a C1-C6 alkoxy group, a C3-C7 cycloalkyl group optionally having 1 to 3 substituents selected from substituent group β, an amino group, a mono- or di-(C1-C6 alkyl)amino group, an aryl group optionally having 1 to 3 substituents selected from substituent group β, and a heteroaryl group optionally having 1 to 3 substituents selected from substituent group β,substituent group β is the group consisting of a halogen atom, a hydroxyl group, a C1-C6 alkyl group and a C1-C6 alkoxy group, m is an integer of 0 to 3,R2 are the same or different and each is a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 alkoxy C1-C6 alkyl group,n is an integer of 0 to 4,R3 are the same or different and each is a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 alkoxy C1-C6 alkyl group,R4 and R5 are each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 alkoxy C1-C6 alkyl group,R6 is —C(O)OR6a, —C(O)—R6b or —S(O)2—R6c,R6a is a C1-C6 alkyl group optionally having 1 to 3 substituents selected from substituent group α, a C3-C7 cycloalkyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkynyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkenyl group optionally having 1 to 3 substituents selected from substituent group β, an aryl group optionally having 1 to 3 substituents selected from substituent group β, or a heteroaryl group optionally having 1 to 3 substituents selected from substituent group β,R6b is a C1-C6 alkyl group optionally having 1 to 3 substituents selected from substituent group α, a C3-C7 cycloalkyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkynyl group optionally having 1 to 3 substituents selected from substituent group β, a C2-C6 alkenyl group optionally having 1 to 3 substituents selected from substituent group β, an amino group, a mono- or di-(C1-C6 alkyl)amino group, an aryl group optionally having 1 to 3 substituents selected from substituent group β, or a heteroaryl group optionally having 1 to 3 substituents selected from substituent group β,R6c is a C1-C6 alkyl group, andR7 is a hydrogen atom, a halogen atom or a C1-C6 alkyl group(see patent document 7).
However, none of the documents report on the fused heterocyclic compound of the present invention.